A. Field of the Invention
The invention generally relates to the field of medicine. More particularly, it concerns the use of dendritic cell vaccines in immunotherapy of breast cancer. In certain aspects, the dendritic cells display cyclin B1 and WT-1 peptide epitopes and are administered to breast cancer patients.
B. Background
Women with breast cancer who are treated with preoperative chemotherapy have the same survival as those who receive adjuvant therapy; however, pathologic complete response (pCR) after preoperative chemotherapy is a predictor of improved outcomes (Fisher, et al., 1997; Rastrogi, et al., 2008). Those treated with preoperative therapy who achieve a pCR or near pCR have significantly better distant relapse-free survival than those with extensive residual disease independent of pathologic subtype.
Women with triple-negative breast cancer (TNBC) have an increased pCR rate as compared to women with non-TNBC, and those with pCR have a 90% disease-free survival (Liedtke, et al., 2008; Von Minckwitz, et al., 2011). However, women with TNBC who do not achieve a pCR (i.e., those that have residual disease after neoadjuvant chemotherapy) have an increased risk of recurrence, decreased overall survival, and post-recurrence survival as compared to women with non-TNBC who do not achieve a pCR. The risk of recurrence and death is time-dependent and significantly higher for women with TNBC in the first 3 years of follow-up, versus women with non-TNBC (Liedtke, et al., 2008).
These patients have a great unmet medical need as there is no known effective therapy which can improve outcome. Therefore, a high priority for clinical research in patients with locally advanced TNBC is to increase the pathologic complete response (pCR) rate in breast and axilla following preoperative therapy. Patients with T3 and T4 cancers and with clinically N1/N2 axillary disease are at highest risk of not achieving a pCR with standard therapy, and of developing metastatic disease.